RESUMEN
A natural compound contained in olive oil, 3,4-dihydroxyphenylethanol (DOPE), is also known as an endogenous metabolite of dopamine. The role of DOPE in oxidative stress-induced cell damage was investigated using differentiated PC12 cells. Superoxide (O(2)(-)) and H(2)O(2) induced a dose-dependent leakage of lactate dehydrogenase (LDH) and decreased cell viability denoted by MTT assay. While O(2)(-) -induced cell damage was not affected by DOPE, pretreatment of the cells with DOPE dose-dependently prevented the leakage of LDH induced by H(2)O(2). In these cells, augmented activity of catalase was demonstrated, while the levels of glutathione and glutathione peroxidase activity remained unchanged. The effect of DOPE was abolished when an inhibitor of catalase 3-amino-l, 2,4-triazole, was included in the medium. DOPE also protected against cell damage induced by H(2)O(2), and Fe(2+). In the hydroxyl radical ((.-)OH) assay using p-nitroso-N, N-dimethylaniline (PNDA), oxidation of PNDA by (.-)OH generated by the Fenton reaction was significantly attenuated in the presence of DOPE. By an electron spin resonance spin trapping study that represents the direct activity of DOPE to scavenge (.-)OH, however, limited scavenging activity was demonstrated for DOPE. Taken together, DOPE may act as a unique cytoprotective compound in nerve tissue subjected to oxidative stress.
Asunto(s)
Muerte Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Dopamina/metabolismo , Estrés Oxidativo/efectos de los fármacos , Alcohol Feniletílico/análogos & derivados , Alcohol Feniletílico/metabolismo , Amitrol (Herbicida)/farmacología , Animales , Catalasa/metabolismo , Muerte Celular/fisiología , Supervivencia Celular/fisiología , Espectroscopía de Resonancia por Spin del Electrón , Inhibidores Enzimáticos/farmacología , Glutatión/metabolismo , Glutatión Peroxidasa/metabolismo , Peróxido de Hidrógeno/toxicidad , Hierro/toxicidad , L-Lactato Deshidrogenasa/metabolismo , Compuestos Nitrosos/química , Estrés Oxidativo/fisiología , Células PC12 , Ratas , Superóxidos/toxicidadRESUMEN
3,4-dihydroxyphenylacetaldehyde (DOPALD), an oxidative metabolite of dopamine (DA), induced dose-dependent DA release from pheochromocytoma (PC12) cells without affecting leakage of lactate dehydrogenase from the cells. DOPALD-induced DA release was independent of extracellular Ca2+ concentration and was not blocked by nifedipine, an L-type Ca2+ channel antagonist. These results indicated a novel intrinsic role of DOPALD in dopaminergic nerve terminals that may take part in the activation of dopamine neurons.